Many HIV-infected patients use herbal products, nutritional supplements, and recreational drugs on a regular basis. The potential for these compounds to interfere with the metabolism of antiretroviral medications or alter the immune system is not well characterized. Last year, we learned of possible significant negative interactions between indinavir (Crixivan) and the commonly used herbal supplement, St John's Wort. In this context, the possibility that the active components of marijuana could interact with the cytochrome P450 system has raised concerns. This type of interaction could have the effect of altering the drug levels of many HIV medications.

Donald Abrams and colleagues at the San Francisco General Hospital conducted this study to characterize the effects of inhaled marijuana or dronabinol (Marinol, an oral pill form) on HIV viral load, immune markers and testosterone levels in patients taking a protease-inhibitor-containing regimen. Sixty-seven patients were enrolled in this 21-day inpatient study. Patients were randomized to receive marijuana cigarettes, dronabinol 2.5mg, or placebo three times a day. Subjects had to be on a stable, protease regimen with stable viral load. Eighty-nine percent of patients were male, median CD4 count 340 and viral load less than 50. There was no significant change in HIV plasma viral load, CD4 or CD8 count during the study. A small decrease in testosterone levels was seen among patients receiving either the marijuana or dronabinol, but not placebo. In sum, this well-designed study shows conclusively that there is no significant immunologic or virologic impact of marijuana in persons with HIV infection. A statistically non-significant decline in testosterone levels was observed and may deserve additional attention.

Change in:

Marijuana(n=20)

Dronabinol(n=22)

Placebo(n=20)

Viral load

0

0

0

CD4 count

29

28

1

CD8 count

181

60

18

Testosterone

-43

-53

11

In a companion presentation (abstract 745), the authors evaluated the pharmacokinetics (drug levels) of either nelfinavir or indinavir. Detailed measurements of drug levels were measured as part of the study. There was a small, but statistically significant decrease in the eight-hour area under the curve (AUC), maximum concentration (Cmax) and minimum concentration (Cmin) of both indinavir and nelfinavir among subjects who smoked marijuana. This decrease was not seen among the subjects who took dronabinol or placebo. It is important to note that study analyzed the short-term virologic and immunologic consequences of marijuana; there is no effect of these inhaled marijuana-induced reductions in drug levels. The long-term aspects are less clear.

Change in pharmacokinetics among patients smoking marijuana:

AUC

Cmax

Cmin

Indinavir

-24%

-21%

-22%

Nelfinavir

-17%

-14%

-17%

These studies are of immediate relevance to the treatment community. Many of my patients use marijuana either recreationally or to offset the side effects of HIV and/or medications. The knowledge that the use of marijuana or it's derivatives will not have significant adverse on the immune system or protease inhibitor levels is reassuring. However, decreases in drug levels deserve some attention, particularly among heavy marijuana smokers. In addition, while it might be reasonable to extend these observations to include other HIV medications, readers should be cautioned to note that the data does not comment on drug-drug interactions with non-nukes or on the viral load in patients taking non-nuke therapy.

This article was provided by TheBodyPRO.com. It is a part of the publication The 8th Conference on Retroviruses and Opportunistic Infections.

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